Mycophenolate mofetil in stable liver transplant patients with calcineurin inhibitor-induced renal impairment

Garcia, Christian Evangelista; Ribeiro, Henrique Barbosa; Garcia, Raphael Moura; Copstein, J; Padilla, Jorge; Santos, Telma; Amaral, do; Silva, A.O; D’Albuquerque, Luiz Augusto Carneiro

doi:10.1016/s0041-1345(03)00337-3

Cited by 8 publications

(6 citation statements)

References 5 publications

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“…In our study, conversion of patients from CI to MMF resulted in improvement in renal function. Those patients who did not require dialysis had either stable or improved renal function, and our data are consistent with the observations made by many other investigators9–12, 31 who have shown improvement in renal function upon withdrawal of CI. Of the 4 patients who required dialysis before or after conversion to MMF, 3 were felt clinically and/or pathologically to have renal failure due to CI.…”

Section: Discussionsupporting

confidence: 92%

“…The role of MMF in the liver transplant population has traditionally been in the immediate posttransplant period. However, recently it has been used as a CI‐sparing drug in patients who developed renal insufficiency 9–12. Although MMF monotherapy is a very attractive option for liver transplant recipients, the efficacy of MMF as monotherapy has been questioned.…”

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confidence: 99%

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Mycophenolate mofetil monotherapy in liver transplant recipients: A single center experience

Fairbanks

Thuluvath

2004

Liver Transpl

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The long-term use of calcineurin inhibitors (CIs) is associated with significant morbidity in liver transplant recipients. Although mycophenolate mofetil (MMF) is well tolerated, two small studies reported an unacceptable rate of acute allograft rejection in liver transplant recipients receiving MMF monotherapy. In this study, we retrospectively investigated the safety and efficacy of MMF monotherapy in liver transplant recipients. We reviewed the medical records of all patients who underwent liver transplant at our institution. Sixteen patients were identified who received MMF either as monotherapy (n ‫؍‬ 13) or with corticosteroids (n ‫؍‬ 3; 2 of them for other comorbid conditions), and these patients were studied to determine the efficacy and complications. Fifteen (15/16) patients were converted from a CI to MMF because of renal insufficiency. Patients were converted to MMF monotherapy after a median of 2,056 days (range, 606-5,893) after liver transplantation. The median postconversion follow-up was 668 days (range, 60-1,509). Four patients required dialysis despite conversion; of those patients not requiring dialysis, serum creatinine stabilized and showed a trend toward improvement (2.51 ؎ 1.12 mg/dL to 1.85 ؎ .58 mg/dL, P ‫؍‬ .1). However, there were 3 episodes (47, 107, and 1,203 days after conversion) of severe, irreversible allograft rejection after conversion resulting in death in 2 patients and necessitating retransplantation in 1 patient. There were no patient characteristics, except perhaps African-American race, that predicted the development of rejection. In conclusion, MMF monotherapy was associated with a significant risk (19%) of unpredictable, severe, and irreversible allograft rejection even among long-term transplant survivors. Caution should be exercised before converting patients to MMF monotherapy. (Liver

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Section: Discussionsupporting

confidence: 92%

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confidence: 99%

Mycophenolate mofetil monotherapy in liver transplant recipients: A single center experience

Fairbanks

Thuluvath

2004

Liver Transpl

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“…The inclusion criteria were: recipients younger than 18 yr, stable liver function tests with at least 12 months of transplantation, no acute rejection at least six months before the study, no chronic rejection biopsy-proven in the last six months and no renal disease before transplantation. Renal dysfunction was defined as: creatinine clearance of <80 mL/min (normal range: 80-120), serum creatinine level >1.0 mg/dL (normal range: 0.3-1.0), azotemia (BUN) >21 mg/dL (normal range: 9-21) and uric acid concentration ‡6.5 mg/dL (normal range: [3][4][5][6]. None of the patients had hypertension at the initiation of the study.…”

Section: Methodsmentioning

confidence: 99%

“…In the cell cycle, MMF acts later than CNIs and may act synergistically with them (3). Because of these advantages, MMF has been increasingly used after OLT in adults and children in order to promote decreased risks of toxic side effects of CNIs (4)(5)(6)(7)(8). However, few studies have evaluated the long-term use of this drug in children with renal dysfunction.…”

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confidence: 99%

Mycophenolate mofetil promotes prolonged improvement of renal dysfunction after pediatric liver transplantation: Experience of a single center

Tannuri

Gibelli

Maksoud‐Filho

et al. 2006

Pediatric Transplantation

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Few studies have evaluated the long-term use of MMF in liver transplanted children with renal dysfunction. The aim of this study is to report the experience of a pediatric transplantation center on the efficacy and security of long-term use of a MMF immunosuppressant protocol with reduced doses of CNIs in stable liver transplanted children with renal dysfunction secondary to prolonged use of CsA or Tac. Between 1988 and 2003, 191 children underwent OLT and 11 patients developed renal dysfunction secondary to CNIs toxicity as evaluated by biochemical renal function parameters. The interval between liver transplantation and the introduction of the protocol varied from one to 12 yr. Renal function was evaluated by biochemical parameters in five phases: immediately prior to MMF administration; 3, 6, 12 and 24 months after the introduction of MMF. Among the patients, nine of them (82%) showed improvement of renal function parameters in comparison with the pretreatment values. The two patients that did not show any improvement were patients in whom the interval of time between OLT and the introduction of MMF was longer. All parameters of liver function remained unchanged. No episodes of acute or chronic rejection or increases in infection rates during the period were detected. Two patients developed transitory diarrhea and leukopenia that were reverted with reduction of MMF dosage. In conclusion, in liver transplanted pediatric patients with CNI-induced chronic renal dysfunction, the administration of MMF in addition to reduced doses of CNIs promotes long-term improvement in renal function parameters with no additional risks.

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“…Various CNI‐sparing immunosuppressive strategies have been explored in liver transplant recipients who exhibit deteriorating renal function while on CNI therapy. Small prospective studies have indicated that the introduction of mycophenolic acid (MPA) with CNI reduction or elimination can improve or even normalize limited renal function in many patients 9–13. Complete withdrawal of CNI therapy in MPA‐treated patients, however, is associated with an increased risk of acute rejection9, 10: in a study of 28 liver transplant recipients with renal dysfunction in whom CNI was withdrawn and replaced with MPA monotherapy, there was a 21% incidence of rejection within the following 6 months versus no rejection episodes in controls who remained on a CNI 9.…”

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confidence: 99%

Incidence and natural course of fatty liver in the general population: The Dionysos study

Bedogni¹,

Miglioli²,

Masutti³

et al. 2007

Hepatology

207

131

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Using the general population of the Dionysos Study, we followed up 144 subjects without fatty liver (FL ؊ ) and 336 with fatty liver (FL ؉ ) for a median time of 8.5 years. All subjects had suspected liver disease (SLD) defined as altered liver enzymes, high mean corpuscular volume, or low platelet count in the absence of HBV and HCV infection. Ethanol intake was assessed using a food frequency questionnaire, and FL was diagnosed using ultrasonography. The incidence and remission rates of FL were 18.5 and 55.0 per 1,000 person-years. Progression to cirrhosis or HCC was rare in both cohorts (incidence rate: 1.7 versus 1.1 and 0.8 versus 0.4 per 1,000 person-years for FL ؊ versus FL ؉ ). Multivariable Poisson regression was performed to identify predictors of FL incidence and remission among sex, age, body mass index, ethanol, and liver enzymes. Every increase of 20 g/day of ethanol intake at baseline was associated with a 17% increase in the rate of incident FL (P ‫؍‬ 0.019), a 10% decrease in the rate of remitting FL and SLD (P ‫؍‬ 0.043), a 19% decrease in the rate of remitting FL with persistent SLD (P ‫؍‬ 0.002), and a 10% increase in mortality rate (P ‫؍‬ 0.005) in the FL ؉ cohort. Conclusion: In the general population of the Dionysos Study, FL regressed in nearly 1 of every 2 cases and had a substantially benign course. Ethanol intake was the most important risk factor for FL remission and incidence and a predictor of mortality in subjects with FL. (HEPATOLOGY 2007;46:1387-1391 R ecent studies performed in representative samples of the general population have shown that fatty liver (FL) is highly prevalent and that anthropometric and metabolic indicators are better predictors of FL than ethanol intake. 1-4 Data are still lacking, however, on the incidence and natural course of FL in the general population. 5 The incidence and remission rates of nonalcoholic fatty liver disease (NAFLD) were 10% and 16%, respectively, in a convenience sample of 4,401 Japanese employees followed for a mean time of 1.1 years. 6 The survival of a community-based sample of NAFLD patients was lower than that of the general population (standardized mortality rate [SMR], 1.34; 95% CI, 1.003-1.76) and 5% of them developed cirrhosis after a mean (SD) time of 7.6 (4.0) years. 7 In the largest clinical study performed to date, 5% of a convenience sample of 129 hospitalized NAFLD patients developed end-stage liver disease after a mean follow-up time of 13.7 years. 8 Referral bias may be responsible for the relatively high incidence of cirrhosis observed in community-and hospitalbased cohorts. 5,7,9 Indeed, there is an ongoing controversy as to whether NAFLD should be considered a benign disease. 10,11 Using data from the follow-up of the Dionysos Study, we evaluated the incidence and natural course of FL in a representative sample of the general population. Patients and MethodsStudy Design. The purpose of the Dionysos Study was to assess the prevalence, incidence, and natural course of liver disease in the general population of 2 towns o...

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Mycophenolate mofetil in stable liver transplant patients with calcineurin inhibitor-induced renal impairment

Cited by 8 publications

References 5 publications

Mycophenolate mofetil monotherapy in liver transplant recipients: A single center experience

Mycophenolate mofetil monotherapy in liver transplant recipients: A single center experience

Mycophenolate mofetil promotes prolonged improvement of renal dysfunction after pediatric liver transplantation: Experience of a single center

Incidence and natural course of fatty liver in the general population: The Dionysos study

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